Download Skin Galenic texture - La Fondation pour la Dermatite Atopique

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APPENDICES
Galenic definitions
EMOLLIENT
This is a raw material or substance that makes the skin softer and suppler, and
improves the characteristics of a cream (long-lasting effect, spreading power,
slippery feel, stickiness, etc.) These emollients are different chemically and can be
more hydrophilic (water soluble), light and non-sticky, or more lipophilic (oil soluble)
and therefore more oily and rich.
They can thus act as moisturizing agents or nourishing agents. They help restore the
skin’s physiological balance and maintain the hydrolipidic film.
E.g.: capric caprylic triglyceride, squalane, vegetable oils, paraffin oil, isopropyl
palmitate, glycerin, etc.
MOISTURIZING AGENT OR HUMECTANT
The role of a moisturizing agent is to improve or restore hydration in the skin. The
moisturizing agent will either retain or transport water since its molecules capture
the water in the skin or in the formula (e.g.: glycerin, sorbitol, propylene glycol, NMF
and intercellular cement components, urea). Another possibility is through a more
mechanical action, where one occlusive molecule can have moisturizing properties
by preventing the water from escaping from the skin (anti-dehydrating).
E.g.: vaseline, mineral oil, silicone…
NOURISHING AGENT
Agent that helps compensate for the skin’s natural lipid deficiency, and helps
strengthen the skin structure, i.e. improve cohesion in the intercellular cement and
thus avoid water loss and skin alteration (e.g.: vegetable oils rich in essential fatty
acids (safflower, evening primrose, avocado, hazelnut, etc.) Triglycerides, shea butter,
lipid components for the epidermis (sterols, waxes, etc.).
Skin
and
Galenic texture
ACKNOWLEDGMENTS
Laure Moulis: Galenic technician, R&D design Vigoulet Pierre Fabre
and Daniel Redoules: Head of «Clinical Pharmacology» Department, Pierre Fabre
Copyright Foundation for Atopic Dermatitis, Doctor Chantal Ségard
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VERVIEW OF ANATOMY
O
AND PHYSIOPATHOLOGY
The skin is the largest organ of the human body: it makes up 16% of its total weight.
Composed of several layers of tissues, it forms a protective barrier for the body
against the external environment, but also guarantees other vital functions.
From a chemical point of view, the skin includes on average:
- 70% water
- 27.5% proteins
- 2% fatty substances
- 0.5% mineral salts and trace elements
It is composed of three tissue layers:
- the epidermis, the uppermost layer
- the dermis, the middle layer
- the hypodermis, the deepest layer
This lipid matrix is composed of ceramides, cholesterol and fatty acids that form a
successive stack of lamellar phases positioned parallel to the skin’s surface.
Keratinocyte differentiation is accompanied by radical changes to their lipid
metabolism and by the lipid composition of the different epidermal layers.
Stratum corneum
Brick wall structure
Components
Corneocytes
Intercorneocyte
lamellar lipids
Components
Bricks
Cement
The epidermis is characterized by its organization in layers, corresponding to an
increasing state of keratinocyte differentiation, from the deepest layer (stratum
basale) to the uppermost layer (stratum corneum), within which anucleated elements
(corneocytes) are included in the multi-lamellar extracellular lipid structure, the
intercorneocyte cement, which acts as a hydric barrier for the skin.
The intercellular cement always contains the same components in varying quantity
and quality.
The main role of the ceramides, some of which are found only on this level, in the
function of the skin’s hydric barrier, is debated in relation to the structural details that
it produces in the intercorneocyte lipid barrier.
DIAGRAM OF EPIDERMAL STRUCTURE
Stratum corneum
Stratum granulosum
Stratum spinosum
Basal layer
Appearance of the Stratum Corneum
under electronic microscope (x 1 200)
According to
Goldsmith L.A.
1991 Oxford
University Press
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Lipid structures in multisheets between
two corneocytes (x 300 000)
According to
Swartzendruber
D.C., et coll. J.
Invest Dermatol,
1989, 134:
460-464
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Table 1. Evolution of the percentage of various lipids based on gradual keratinocyte differentiation, from the
deepest area (basal/spinous) to the uppermost cornified layer, and also the granular layer, where the lipids are
stored within the Odland bodies. We observe a drop in phospholipid levels, an increase in ceramides, free fatty
acids and non-esterified sterols, as well as the highest level of glucosylceramides (acylglucosylceramides) in the
granular layer (where they contribute to the stacked lipid structures) and they practically disappear in the cornified
layer (according to Lampe et al. [40]).
Composition
Basal/Spinous
Granular layer
Cornified layer
Phospholipids
44.5 ± 3.4
25.3 ± 2.6
6.6 ± 2.2
Cholesterol sulfate
2.6 ± 3.4
5.5 ± 1.3
2.0 ± 0.3
Neutral lipids
51.0 ± 4.5
56.5 ± 2.8
66.9 ± 4.8
Free sterols
11.2 ± 1.7
11.5 ± 1.1
18.9 ± 1.5
Free fatty acids
7.0 ± 2.1
9.2 ± 1.5
26.0 ± 5.0
Triglycerides
12.4 ± 2.9
24.7 ± 4.0
Variable
Sterol/fatty esters
5.3 ± 1.3
4.7 ± 0.7
7.3 ± 1.2
Squalene
4.9 ± 1.1
4.6 ± 1.0
6.5 ± 2.7
n-alkanes
3.9 ± 0.3
3.8 ± 0.8
8.2 ± 3.5
Sphingolipids
7.3 ± 1.0
11.7 ± 2.7
Glucosylceramides
3.5 ± 0.3
5.8 ± 0.2
Trace
Ceramides
3.8 ± 0.2
8.8 ± 0.2
24.4 ± 3.8
99.1
101.1
99.9
Total
Water mobility in the skin makes up the hydration and dehydration mechanisms.
The water spreads passively from the Malpighi layer to the cornified layer, and
then passes through the cornified layer to the exterior. This diffusion is invisible, and
is referred to as insensible perspiration or transepidermal water loss (T.E.W.L.).
Under normal conditions, with a whole skin barrier, T.E.W.L. occurs at 5gr/m²/hour.
Transepidermal water loss must not be confused with perspiration and sebaceous
secretion, which are different processes.
Factors retaining water in the cornified layer.
These are intracellular substances called "Natural Moisturizing Factors" or N.M.F.
They are formed during the transformation of keratinocytes into corneocytes within
the granular layer, and during the transformation of Profilaggrin into Filaggrin. N.M.F.s
are composed of Urea, amino acids, pyrrolidone carboxylic acids, lactic acids,
mineral ions, sugars (Hexoses, pentoses).
WATER CONCENTRATION GRADIENT
Air
24.4 ± 3.8
According to John Libbey text. Article by Jean-Claude Mazières 2007
H2O
Water
WATER AND THE SKIN
The skin forms an interface between the body and the outside environment, and it
therefore fulfills not only a protective role against the penetration of chemical or microbial
elements, but it must also guarantee stability of the body’s physiological environment
by limiting water loss. To do so, the uppermost layer of the epidermis, the
stratum corneum, plays a major role in osmotic homeostasis whose function
is to maintain a hydric gradient and thus reduce the drying effects caused by the
environment. Under physiological conditions, the water content of the upper layer of
the epidermis varies from 70 to 30% from the last living layers (stratum granulosum)
to the stratum corneum. Water content is even lower in the last corneocyte layers,
reaching 15%.
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This capacity to maintain hydric balance comes directly from the structure of the
stratum corneum, by its flattened keratinized cells, the corneocytes, stacked within
a lipid matrix composed of ceramides, cholesterol and fatty acids as we discussed
earlier.
In a state of dryness, the water content in the upper layers decreases and the stratum
corneum has a tendency to retract and to lose its mechanical properties. The skin
becomes hard and rough, causing a sensation of discomfort and tightness. At a
more severe stage, the stratum corneum loses its barrier quality, which triggers the
following responses in particular: increase in intra-epidermal perspiration, excessive
keratinocyte proliferation, modification of supramolecular arrangement in the lipid
matrix. Clinically, the skin becomes thicker and squamous, making it more prone to
cracking.
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Links between the Stratum Corneum (cornified layer), transepidermal water
loss and the skin barrier.
If the Stratum Corneum is altered by a dermatological condition or external aggression,
this causes a loss in porosity and an increase in Transepidermal Water Loss. For atopic
skin, (on non-eczematous dry skin) TEWL occurs at 18 gr/m²/hour compared to 5
gr/m²/hour in normal skin. The same rate is observed in normal skin if the outside
temperature is high with low humidity. Transepidermal Water Loss is a reflection of
the condition of the skin barrier.
THE HYDROLIPIDIC FILM
The hydrolipidic film is found on the skin’s surface, and it supports the concept of a
barrier, participating in exchanges between the skin and the outer environment.
The skin’s surface is covered by what is called a hydrolipidic film, namely an
emulsion of water (hydro) and fat (lipos). Its main function is to act as an external
barrier to defend the body against bacteria and fungi. Moreover, it keeps the skin
supple. In healthy skin, the balance
between the fatty component
and the aqueous component
remains intact. The quantity and
composition of the hydrolipidic film
varies according to body parts but
also according to exogenous and
endogenous factors such as time
of day, season, air humidity, diet,
stress and disease.
Composition of the hydrolipidic film
Analysis of the skin’s structure and of the keratinization process indicates the presence
of the following substances on the skin’s surface:
• Perspiration and sebaceous lipids
• Substances from the cornification process (protein breakdown substances)
• Cornified cells detaching themselves
• Water from the deepest layers arriving at the surface (transepidermal water, insensible
perspiration)
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The following components form a protective film on the skin’s surface that is
continuously renewed:
1 • Perspiration
2 • Sebaceous lipids
3 • Corneocytes detaching themselves
4 • Cells undergoing cornification
5 • Transepidermal water
One of the functions of the hydrolipidic film is to repel foreign bodies. It also helps
maintain the skin’s suppleness. Thanks to the presence of mildly acidic components,
such as lactic acid, pyrrolidone carboxylic acid and amino acids, the hydrophilic
components of the hydrolipidic film can form an acidic protective cloak.
RY SKIN, DEHYDRATED SKIN
D
AND STEPS TO BE TAKEN
The quality of the epidermal components and those of the hydrolipidic film therefore
determine the various conditions of the skin. This is described as dry skin or
dehydrated skin.
• DRY SKIN
In dry skin, the hydrolipidic film has not fulfilled its role; there is more water evaporation
and not enough lipids in the epidermis. The skin is thin, smooth and dull, fragile and
delicate with wrinkles and fine lines showing up early. The skin feels tight, does not
tolerate soap and reddens easily in the cold. Dry skin will always become dehydrated
if no action is taken.
This condition comes from insufficient sebaceous secretions (sweat) due to genetic
factors, ichthyosis, climate or the use of detergents and harsh products.
• DEHYDRATED SKIN
Dehydrated skin lacks water, and can affect all types of skin. This is a reversible
condition, with various origins (wind, cold, excess sun, lack of humidity in the
atmosphere, detergent products, etc.). Dehydrated skin still has its hydrolipidic film,
and water loss is more in-depth. The skin is dull, lacking radiance, rough, lacking
suppleness, fragile, irritable and it wrinkles easily. It then tends to desquamate and
become dry but it is possible to have dehydrated skin that is not very dry.
• TREATING DRYNESS
We can hydrate the skin but however water cannot be added directly to the inside of
the skin; water cannot penetrate the skin by itself!
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The water must be transported via glycerides
which intervene through the hydrolipidic film
and penetrate the upper layers, or through the
Stratum Corneum (SC) with water-retaining
molecules, to reduce transepidermal water loss
and thus increase water content.
There are therefore 2 possibilities:
- Retain the water already contained in the skin, whether on the surface (the role of
the hydrolipidic film) or in the deeper layers (the role of the intercellular cement).
- Allow water in the deep layers to travel up to the surface when needed (role of the
intercellular cement and the cell membranes).
The outermost layers of the SC can thus be strengthened with vaseline by example,
since its long-chain C-26 structure falls into place in the ceramidic bilayers of the
stratum corneum. This practically occlusive action induces a reduction in water
evaporation through the stratum corneum. Similar actions can be obtained by using
symmetrical long-chain esters, which have the advantage of being less occlusive
than vaseline and therefore more pleasant to use. Among the most well known are
myristyl myristate, cetyl palmitate and isostearyl isostearate. These approaches aim
to strengthen the functional aspect of the intercorneocyte lipids under conditions
of dryness, and are generally combined in emulsions with hygroscopic humectants
(which retain water) such as glycerol, urea, sorbitol and others.
We can therefore classify the moisturizing agents into 3 sub groups based on their
lipophilic characteristics.
• occlusive agents, which reduce transepidermal water loss,
• emollients, which are partially occlusive and which fill the intercorneocyte spaces,
• humectants, which are hygroscopic and capable of absorbing water from their
surroundings.
A cosmetic product containing a high proportion of occlusive agents can be
considered to be oily. After adding an emollient with excellent spreading power, the
finished product will be noticeably improved in terms of texture and sensation when
applied.
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GALENIC FORMS
Galenic terminology (in the literal sense of the term) is different to marketing
terminology.
It’s all about emulsion!
- The "cream" and "fluid" forms are void of terminological significance, since these are
in fact emulsions.
- The "cream" form suggests a rich emulsion whereas the "fluid" form suggests a light
emulsion.
- The "serum" form is not a galenic form; it is a relatively thick lotion, gel or emulsion
highly concentrated in active principles..
"PHYSICAL" DEFINITION OF AN EMULSION
Homogenous mixture resulting from the dispersion of two
immiscible non-homogenous phases of different types.
To obtain a smooth final product, stabilization must be
permitted for the two-phase mixture through an emulsifier
or a surfactant.
• TWO TYPES OF EMULSIONS
- Oil-in-water: drops of oil (oily phase) are
suspended in water (aqueous phase); the water
forms the continuous phase which gives it its
hydrating properties, hence the name continuous
aqueous phase.
Water
Oil
Emulsifier
Oil
- Water-in-oil: drops of water (aqueous
phase) are trapped in oil (oily phase) forming
a continuous film. A lipid film is created on the
skin, hence the long-lasting properties and
the "barrier effect".
Water
Emulsifier
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The difference between W/O and O/W emulsions is not visible macroscopically or
microscopically. The difference is in their spreading power, cosmetic qualities,
cosmetic appeal, and the sensation upon application.
O/W emulsions are easier to spread; they have more slip and a more aqueous,
"wet" feel. They are also lighter and more fleeting in composition than the W/O
emulsions which require more massaging action to be absorbed into the skin, leaving
a sensation of oil or butter and a more shiny, sticky appearance with a heavy feel.
There are fewer W/O than O/W emulsions because of these poor cosmetic qualities
(stickiness, difficulty to spread) and their feasibility and stability. O/W emulsions are
preferred since all these factors can be modified by adapting the composition. There
is a wide range of raw materials that allow us to modify a formula’s feel, texture and
visual appearance.
What’s also important is the choice of emulsifier that structures the formula and can
transport its water content or emollients, reservoir system (emulsifier forming liquid
crystals or spherulites, etc.) to the core of the epidermis.
• DIFFERENT TYPES OF TEXTURES FOR THESE EMULSIONS:
LOTION, EMULSION, CREAM, BALM...
Lipid content is in descending order: water-in-oil W/O balms, oil-in-water O/W rich in
oils, oil-in-water less rich in oils.
Lotions and milks with a large proportion of water and a small quantity of glycerides.
The difference is also in the product’s viscosity, the natural composition and oily
phase content and the relatively "oily" sensation especially on the fingertips and when
spreading.
For light textures (lotion, emulsion): preference is given to lightweight emulsifiers
or emulsifying gelling agents with oily phase content of 5 to 15% composed of
emollients light to the touch, non greasy, non oily, non sticky with good "slip" without
too many sticky glycols or vaseline-type oils.
For rich textures (cream, balm): preference is given to more waxy emulsifiers, to
which oily emollients are added with a rich greasy feel, such as shea butter, paraffin
derivatives, evening primrose oil, safflower oil, beeswax and often high content in
glycerin and vaseline, the % of these oily phases can reach 40 or 50% of the
product’s composition.
- LOTION: the texture is fluid to very fluid (flows easily), non oily, generally oil in
water, allowing it to be spread easily over the entire body without too much oily
residue (non filmogenic) or sticky effect. The product is rapidly absorbed, leaving
an "aqueous", "wet" sensation. It contains light emollient agents that have no sticky
effect, no greasy oil, wax or butter, and often with gel-like textures that provide the
light feel. Hydrating properties claimed but with a low glycol level to always limit the
sticky effect and facilitate rapid absorption.
- EMULSION: this is a light, fine texture that does not contain a large oily phase
or emollients with a rather light feel, less fluid than the lotion. The formula is often
designed for the face, and stays put on the fingertips, and is rapidly absorbed. Used
for hydration claims, for oily or combination skin. Emulsions are similar to lotions in
terms of formula and composition of the oily phase. Sensation of comfort without
residue on the skin and no sticky effect.
- CREAM: the texture of a cream is much more consistent and thicker than an
emulsion. It is richer, smoother, more filmogenic and oilier, and can be W/O or O/W.
Used for relatively significant nourishing claims. Designed for the driest skin types,
in need of nourishment. Anti-dehydration claims, night product or product for atopic
skin.
- BALM: very rich texture with a high level of nourishing (oily) agents and oils, very
filmogenic for very dry, atopic skin. Balms can have varying viscosity (more or less
thick). They have a longer-lasting effect than creams. Very smooth. The product has
to be manipulated while spreading it, and worked into the skin by massaging action.
• CERATE/OINTMENT
Ointments and cerates were initially anhydrous products (without water), a homogenic
monophase mixture of liquid glycerides, miscible pastes and solids (waxes, butters,
oils).
Cerates evolved gradually, and distilled flower water and other similar waters were
introduced to obtain "Galen’s wax", and then a more modern version, COLD CREAM.
These products are extremely rich and oily with a more limited spreading power,
hence their use on smaller areas, sometimes in thick layers for in-depth nourishment.
NOURISHING POWER / "OILY" PHASE CONTENT GRADIENT
LOTION
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EMULSION
CREAM
BALM
CERATE/COLD CREAM
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